A number of devices and methods for determining concentration or presence of one or more analytes in body fluids (e.g., blood, urine and saliva) are known in the art, including blood analyte measurement.
Specifically, test elements are known for rapidly and simply conducting such measurements that use at least one reagent element. Such reagent elements may be configured to carry out at least one detection reaction that is detectable in the presence of the at least one analyte such as, for example, a detection reaction that is optically detectable and/or a detection reaction that is electrochemically detectable. Possible reagent elements that may be used within the scope of this disclosure are disclosed in, for example, Hönes et al. (2008) Diabetes Technol. Ther. 10:10-26; as well as WO Patent Application Publication Nos. 2010/094426 and 2010/094427. A number of different kinds of test elements that include a reagent element also are known in the art. See, e.g., EP Patent Application Publication Nos. 0302287, 0547710 and 1593434.
In addition, EP Patent Application Publication No. 2325624 describes a device and method of assaying a body fluid. The object of the reference is to control a transmittance behavior of an optical transmittance system of a device by measuring at two different wavelengths. The method includes detecting diffuse reflectance curves at two different wavelengths. In the methods, measurement curves are subjected to fitting so that two fit curves are generated. An offset is determined from an intersection of the two fit curves (in the section between t1 and t2 in FIG. 5), and as described in, for example, paragraph [0030], an offset correction of the measurement values is conducted. The offset correction, as described in paragraph [0023], is necessary because the start time of sample application is uncertain and/or imprecise (e.g., paragraphs [0005]-[0006]), the transmittance behavior of the optical transmittance system may change upon applying the body fluid. A change in the reflectance behavior during wetting of the reagent element with the sample is not taken into account, as may be clearly seen in paragraph [0030], and the reflectance behavior during wetting is seen as constant.
U.S. Pat. No. 5,246,858 describes a device and a method of determining a reflectance of a reagent element that reacts with a body fluid component. In the method, the reagent element is irradiated with a radiation source, and the light reflected from the reagent element is determined. As may be seen in column 18, lines 18 ff., threshold value methods may be used to analyze the curve.
U.S. Pat. No. 5,049,487 describes a method of determining a presence of an analyte in a fluid. In the method, a reflectance measurement is conducted on a reagent matrix.
A practical problem frequently occurring in optical detection methods is as follows. While the actual detection reaction shows high specificity (i.e., only takes place in the presence of the analyte to be detected, not in the presence of other kinds of analytes), the detection of the reaction, which takes place based on a change in reflectance of the test field containing the reagent element, is influenced in many cases by one or more disturbance variables (e.g., specifically the percentage of red blood cells in a blood sample, i.e., the hematocrit value). As such, in blood glucose measurements using optical methods, the measurement values can depend on the hematocrit (Hct). This dependency also may be observed in electrochemical systems, which are generally correctable by a conductivity measurement and thus direct measurement of Hct.
Electrochemical devices and methods of analyte detection that take Hct into account are described in US Patent Application Publication No. 2010/0159570. The fill time of a test strip is used to determine the viscosity of the blood, and this in turn is used to determine Hct.
Similarly, JP Patent Application Publication No. 2007303968 describes a method of measuring an analyte in a blood sample that includes Hct correction. In this case, a test element with a filling channel is used, and a fill rate of the filling channel is determined. This fill rate in turn is used to determine Hct.
WO Patent Application Publication No. 2006/138226 describes a device for measuring blood glucose concentrations. In addition, a method is described in which Hct is determined from a time course of a change in a detector signal. Accordingly, a correction factor is selected depending on the Hct to calculate a glucose concentration.
WO Patent Application Publication No. 2008/114060 describes a device and method of determining a target substance in plasma of a whole blood sample without requiring removal of the red blood cells from the plasma prior to the test. In the method, an offset of an optical density is used to determine hemoglobin (Hb) concentration in the sample.
EP Patent Application Publication No. 2259058 describes a device and method of measuring Hct. In this case, a first measurement wavelength is used to determine Hb, and a second measurement wavelength is used to monitor an analyte-dependent color reaction.
U.S. Pat. No. 4,935,346 describes a method of determining presence of an analyte in a fluid sample. In this method, after a start time initiated by wetting, background measurement is conducted for correcting Hct at a preset first measurement time by means of a first light-emitting diode (LED) with a first wavelength of 700 nm. At a second measurement time, a second LED with a wavelength of 635 nm is used to measure glucose, and this measurement is corrected by Hct. In practice, however, this method is relatively expensive and requires a fairly high degree of expenditure on equipment. Optical measurements must be taken at different wavelengths at which the light is influenced differently by the actual detection reaction and Hct. Furthermore, the two optical measurements at different wavelengths are nevertheless influenced respectively by both Hct and blood glucose content. Even simple measurements of a background signal still show a relatively high degree of measurement uncertainty.
The continuing result of Hct dependency seen in conventional systems and methods, particularly photometric systems, is that despite the high operating expenses of known correction methods, the Hct range within which known systems and methods can be used is relatively narrow.
For the foregoing reasons, there is a need for additional devices and methods of determining an analyte concentration even when a disturbance variable is present in the sample.